Unpacking Myhre Syndrome

Have you heard of Myhre syndrome? In this article, we set out in detail what Myhre syndrome is, a rare genetic disorder that affects one person in every million worldwide.

What is Myhre syndrome?

Myhre syndrome is an extremely rare and little-known genetic condition, characterized by a set of specific physical and developmental symptoms and features. It is a genetic disorder that affects multiple body systems. It is believed to be caused by mutations in the SMAD4 gene, which plays a crucial role in cellular signaling and tissue development.

Its prevalence is estimated at approximately one person per million worldwide. In fact, currently there are only about two hundred diagnosed cases globally. In Spain, the number of affected individuals stands at 16 people.

Although it was first discovered and described in the 1980s, today it remains the subject of study to better understand its cause, its manifestations and the best methods of management and treatment.

Genetic and clinical studies are helping to unravel the underlying mechanisms of the condition and to develop better treatment and management strategies.

Causes of Myhre syndrome

Myhre syndrome can be caused by mutations in the SMAD4 gene, which plays a key role in cellular signaling and in regulating the growth and development of various tissues and organs in the body. Mutations in SMAD4 alter the normal function of the protein encoded by this gene, leading to the various clinical manifestations of the syndrome.

Details about the SMAD4 gene

• Function of the SMAD4 gene: the SMAD4 gene encodes a protein that is part of the TGF-beta (transforming growth factor beta) signaling pathway, which is important for the development and maintenance of connective tissue, the regulation of cell growth and the immune response.
• Mutation: the mutations that cause Myhre syndrome are generally de novo, which means they occur for the first time in the affected person and are not inherited from the parents. These mutations are usually point changes in the gene that alter the function of the SMAD4 protein, leading to dysfunction in the cellular signaling pathways regulated by this protein.

Signs and symptoms of Myhre syndrome

Documented cases have allowed the identification of a consistent pattern of symptoms and characteristics.

Myhre syndrome presents a variety of signs and symptoms that affect many parts of the body, although not all people display all possible features.

The most common include short stature, skeletal abnormalities, limited joint mobility, characteristic facial features, intellectual and behavioral problems, hearing loss, a tendency to accumulate scar tissue (fibrosis) in the skin and internal organs, and cardiac and pulmonary abnormalities.

Below we show a classification of them:

Facial and physical features

• Distinctive facial features: individuals with this syndrome often have a characteristic face with features such as a prominent forehead, flat nasal bridge, thin lips and a small jaw (micrognathia).
• Short stature: most patients have a height significantly below the average for their age and sex.
• Joint stiffness: joint stiffness is a common finding, which can lead to limitations in mobility and orthopedic problems. One of the most common difficulties is raising the arms or clenching the fists.
• Ocular abnormalities such as strabismus.

Cognitive deficits

• Delayed motor and speech development: many children with Myhre syndrome experience delays in reaching developmental milestones such as sitting, walking and talking, which can be evident in the early years of life.
• Intellectual disabilities: most affected people have some degree of intellectual disability that may range from mild to moderate or severe.
• Learning difficulties: children with this syndrome may have significant problems with learning in conventional educational settings and their performance in them. These may be related to problems with short-term memory, attention, abstract reasoning, information processing and problem solving.
• Language and communication problems: deficits in language development are common and may include both expressive language problems (difficulty articulating words or forming complex sentences) and receptive language problems (difficulty understanding what they are told, following instructions and participating in conversations).
• Behavioral problems: repetitive, stereotyped or ritual behaviors may be common. Problems with social interaction, similar to those observed in autism spectrum disorders, can also be observed.
• Mental health problems: some of them may experience mental health problems, such as anxiety or depression, due to cognitive and social difficulties. In some cases, they may manifest challenging or disruptive behaviors that require behavioral intervention or psychological support.
• Motor difficulties: fine and gross motor skills may be affected, impacting the ability to perform daily tasks (such as writing or fastening a button) and participate in physical activities. Coordination and balance may also be compromised.

Cardiac and respiratory problems

• Morphological cardiovascular abnormalities: the vast majority of affected individuals may present congenital heart defects that require monitoring and, in some cases, medical intervention.
• Respiratory problems: tissue stiffness can affect lung and respiratory function, causing complications such as sleep apnea or restrictive lung diseases.

Other health problems

• Hearing loss: hearing loss, often due to recurrent otitis media, is a relatively common feature.
• Gastrointestinal problems: some patients experience digestive problems, including gastroesophageal reflux and constipation.

Diagnosis and treatment 

The diagnosis of Myhre syndrome is based on clinical evaluation and can be confirmed by genetic testing that identifies mutations in the SMAD4 gene.

Most cases are diagnosed in infancy or early childhood, due to developmental delays and evident physical characteristics.

Given the complex and multisystem nature of the syndrome, and the fact that there is still no cure, treatment focuses on managing symptoms through a multidisciplinary approach.

Multidisciplinary management

• Regular medical care: regular monitoring by a team of specialists that may include geneticists, cardiologists, orthopedists and speech therapists, among others.
• Therapeutic interventions: physical and occupational therapies can help improve mobility and functionality.
• Educational support: special education programs and classroom support may be necessary to address learning difficulties.

Psychosocial support

Psychosocial support for families is also crucial. Support groups and organizations dedicated to rare diseases can provide valuable resources and an emotional support network for parents and caregivers.

Conclusion

Myhre syndrome, although rare, is a condition that presents significant challenges for those who suffer from it and their families. With appropriate understanding and interdisciplinary management, it is possible to improve the quality of life of these patients. Awareness and ongoing research are essential to continue advancing knowledge and treatment of this complex condition. 

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“This article has been translated. Link to the original article in Spanish:”
Deconstruyendo el síndrome de Myhre